[Federal Register Volume 84, Number 63 (Tuesday, April 2, 2019)]
[Proposed Rules]
[Pages 12534-12537]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-06188]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 610
[Docket No. FDA-2018-N-4757]
RIN 0910-AH95
Revocation of the Test for Mycoplasma
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is
proposing to amend the biologics regulations by removing the specified
test for the presence of Mycoplasma for live virus vaccines and
inactivated virus vaccines produced from in vitro living cell cultures.
FDA is proposing this action because the existing test for Mycoplasma
is restrictive in that it identifies only one test method in detail to
be used even though other methods also may be appropriate. More
sensitive and specific methods exist and are currently being practiced,
and removal of the specific method to test for Mycoplasma provides
flexibility for accommodating new and evolving technology and
capabilities without
[[Page 12535]]
diminishing public health protections. This action is part of FDA's
implementation of Executive Orders 13771 and 13777. Under these
Executive orders, FDA is comprehensively reviewing existing regulations
to identify opportunities for repeal, replacement, or modification that
will result in meaningful burden reduction, while allowing the Agency
to achieve our public health mission and fulfill statutory obligations.
DATES: Submit either electronic or written comments on the proposed
rule by June 17, 2019.
ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. Electronic comments
must be submitted on or before June 17, 2019. The https://www.regulations.gov electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of June 17, 2019. Comments received
by mail/hand delivery/courier (for written/paper submissions) will be
considered timely if they are postmarked or the delivery service
acceptance receipt is on or before that date.
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on https://www.regulations.gov.
If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
Mail/Hand delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2018-N-4757 for ``Revocation of the Test for Mycoplasma.'' Received
comments, those filed in a timely manner (see ADDRESSES), will be
placed in the docket and, except for those submitted as ``Confidential
Submissions,'' publicly viewable at https://www.regulations.gov or at
the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through
Friday.
Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Tami Belouin, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 240-
402-7911.
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Executive Summary
A. Purpose of the Proposed Rule
B. Summary of the Major Provisions of the Proposed Rule
C. Legal Authority
D. Costs and Benefits
II. Background
A. Introduction
B. Need for Regulation
III. Legal Authority
IV. Description of the Proposed Rule
A. Scope
B. Appropriate Controls Would Remain in Place
V. Proposed Effective Date
VI. Economic Analysis of Impacts
VII. Analysis of Environmental Impact
VIII. Paperwork Reduction Act of 1995
IX. Federalism
X. Consultation and Coordination with Indian Tribal Governments
XI. References
I. Executive Summary
A. Purpose of the Proposed Rule
FDA proposes to remove the regulation requiring a specified test
for the presence of Mycoplasma for live virus vaccines produced from in
vitro living cell cultures and inactivated virus vaccines produced from
such living cell cultures because the regulation is restrictive in that
it identifies only one test method in detail to be used even though
other methods also may be appropriate. More sensitive and specific
methods exist and are currently being practiced, and removal of the
required test for Mycoplasma provides flexibility for accommodating new
and evolving technology and capabilities without diminishing public
health protections.
B. Summary of the Major Provisions of the Proposed Rule
The proposed rule removes Sec. [thinsp]610.30 (21 CFR 610.30),
which details the method for Mycoplasma testing of samples of the virus
harvest pool and control fluid pool of live virus vaccines and
inactivated virus vaccines produced from in vitro living cell cultures.
C. Legal Authority
FDA is taking this action under the biological products provisions
of the Public Health Service Act (the PHS Act), and the drugs and
general
[[Page 12536]]
administrative provisions of the Federal Food, Drug, and Cosmetic Act
(FD&C Act).
D. Costs and Benefits
Because this proposed rule would not impose any additional
regulatory burdens, this regulation is not anticipated to result in any
compliance costs and the economic impact is expected to be minimal.
II. Background
A. Introduction
On February 24, 2017, Executive Order 13777, ``Enforcing the
Regulatory Reform Agenda'' (https://www.federalregister.gov/documents/2017/03/01/2017-04107/enforcing-the-regulatory-reform-agenda, 82 FR
12285; March 1, 2017) was issued. One of the provisions in the
Executive order requires Agencies to evaluate existing regulations and
make recommendations to the Agency head regarding their repeal,
replacement, or modification, consistent with applicable law. As part
of this initiative, FDA is proposing to revoke a regulation as
specified in this proposed rule.
B. Need for Regulation
It has become increasingly clear that the test for Mycoplasma
requirements is too restrictive for live virus vaccines and inactivated
virus vaccines produced from in vitro living cell cultures because they
specify particular methodologies when alternatives may be available
that provide the same or greater level of assurance of safety.
Modifications to mycoplasma testing described in Sec. 610.30 must meet
the requirements of 21 CFR 610.9.
Thus, the Agency believes that the regulation may no longer reflect
the current testing procedures as a general matter and that it is more
appropriate, flexible, and efficient to identify appropriate testing
requirements for particular products in the biologics license
application (BLA).
This proposed rule would remove the specified test for the presence
of Mycoplasma to provide flexibility for accommodating new and evolving
technology and capabilities without diminishing public health
protections. Removal of this regulation would allow manufacturers of
live virus vaccines produced from in vitro living cell cultures and
inactivated virus vaccines produced from such living cell cultures to
select the most scientifically appropriate Mycoplasma testing method to
assure the safety, purity, and potency of their vaccines.
These newer technologies can result in higher sensitivity and
specificity of Mycoplasma detection and could reduce the time required
to complete testing for Mycoplasma. Removal of this regulation would
not remove Mycoplasma testing requirements specified in individual
BLAs. A manufacturer of a live virus vaccine produced from in vitro
living cell cultures and inactivated virus vaccines produced from such
living cell cultures would continue to be required to follow the
Mycoplasma test requirements specified in its BLA, unless the BLA were
revised to modify or replace the test through a supplement in
accordance with Sec. [thinsp]601.12(c) (21 CFR 601.12(c)). FDA would
review proposed changes to a manufacturer's approved biologics license
in the context of that particular application to ensure that any such
action is appropriate.
The proposed rule, if finalized, will remove the regulation;
however, a manufacturer would continue to be required to test for
Mycoplasma as specified in its BLA. If finalized, this action will
provide regulated industry with flexibility, as appropriate, to employ
advances in science and technology as they become available, without
diminishing public health protections. As appropriate, the Agency will
describe the appropriate tests for particular products in
manufacturers' BLAs.
III. Legal Authority
FDA is issuing this proposed rule under the biological products
provisions of the PHS Act (42 U.S.C. 216, 262, 263, 263a, and 264) and
the drugs and general administrative provisions of the FD&C Act (21
U.S.C. 321, 331, 351, 352, 353, 355, 360, 360c, 360d, 360h, 360i, 371,
372, 374, and 381). Under these provisions of the PHS Act and the FD&C
Act, we have the authority to issue and enforce regulations designed to
ensure that biological products are safe, pure, and potent, and prevent
the introduction, transmission, and spread of communicable disease.
IV. Description of the Proposed Rule
A. Scope
The test for Mycoplasma in Sec. [thinsp]610.30 is intended to
ensure that live virus vaccines produced from in vitro living cell
cultures, and inactivated virus vaccines produced from such living cell
cultures do not contain Mycoplasma. Currently the regulation details
the method for Mycoplasma testing of samples of the virus harvest pool
and control fluid pool of live virus vaccines and inactivated virus
vaccines produced from in vitro living cell cultures. Removal of this
regulation would eliminate a restrictive and duplicative requirement
and accommodate new and evolving technology.
We are proposing to remove the specified test for the presence of
Mycoplasma for live virus vaccines produced from in vitro living cell
cultures and inactivated virus vaccines produced from such living cell
cultures. FDA is proposing this action because the existing specified
test for the presence of Mycoplasma is restrictive and duplicative of
requirements that are also specified in the BLA. This change is
intended to remove restrictive or duplicative requirements and
accommodate new and evolving technology and capabilities without
diminishing public health protections. Removal of this regulation would
not remove Mycoplasma testing requirements specified in individual
BLAs. A biological product manufacturer would continue to be required
to follow the Mycoplasma testing requirements specified in its BLA
unless the BLA were revised to modify or replace the test through a
supplement in accordance with Sec. 601.12(c). FDA would review
proposed changes to a manufacturer's approved biologics license in the
context of that particular license to ensure that any such action is
appropriate.
FDA is proposing to remove the requirements contained in Sec.
[thinsp]610.30 from the regulations. As a result of removing Sec.
[thinsp]610.30, we would also remove and reserve 21 CFR part 610,
subpart D. FDA is proposing this action because the testing method
described in the regulation is restrictive and more sensitive and
specific testing methods are now available.
B. Appropriate Controls Would Remain in Place
FDA believes that if this rulemaking becomes finalized as proposed,
we would be able to continue to ensure that appropriate controls remain
in place. If the proposed rule is finalized and the regulation calling
for a specific test for Mycoplasma is eliminated, manufacturers would
continue to be required to perform a test for Mycoplasma described in
their BLAs for their licensed live virus vaccines produced from in
vitro living cell cultures and their inactivated virus vaccines
produced from such cultures. Such requirement would remain in effect
unless the BLA were revised to modify or replace the test through a
supplement in accordance with Sec. [thinsp]601.12(c). FDA would review
proposed changes to a manufacturer's approved biologics license in the
context of that particular license to
[[Page 12537]]
ensure that any such action is appropriate.
V. Proposed Effective Date
FDA is proposing that any final rule based on this proposed rule
become effective 30 days after the date of its publication in the
Federal Register.
VI. Economic Analysis of Impacts
We have examined the impacts of the proposed rule under Executive
Order 12866, Executive Order 13563, Executive Order 13771, the
Regulatory Flexibility Act (5 U.S.C. 601-612), and the Unfunded
Mandates Reform Act of 1995 (Pub. L. 104-4). Executive Orders 12866 and
13563 direct us to assess all costs and benefits of available
regulatory alternatives and, when regulation is necessary, to select
regulatory approaches that maximize net benefits (including potential
economic, environmental, public health and safety, and other
advantages; distributive impacts; and equity). Executive Order 13771
requires that the costs associated with significant new regulations
``shall, to the extent permitted by law, be offset by the elimination
of existing costs associated with at least two prior regulations.'' We
believe that this proposed rule is not a significant regulatory action
as defined by Executive Order 12866.
The Regulatory Flexibility Act requires us to analyze regulatory
options that would minimize any significant impact of a rule on small
entities. Because this proposed rule would increase flexibility and
does not add any new regulatory responsibilities, we propose to certify
that the proposed rule will not have a significant economic impact on a
substantial number of small entities.
The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires
us to prepare a written statement, which includes an assessment of
anticipated costs and benefits, before proposing ``any rule that
includes any Federal mandate that may result in the expenditure by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100,000,000 or more (adjusted annually for
inflation) in any one year.'' The current threshold after adjustment
for inflation is $150 million, using the most current (2017) Implicit
Price Deflator for the Gross Domestic Product. This proposed rule would
not result in an expenditure in any year that meets or exceeds this
amount.
We believe industry will largely maintain their current practices
following the removal of Sec. 610.30 Test for Mycoplasma. Although
manufacturers of live virus vaccines and inactivated virus vaccines
produced from in vitro living cell cultures may experience some
unquantifiable cost savings from streamlining their testing procedures,
we predict no quantifiable cost savings. FDA will also maintain its
current practices, similarly generating no quantifiable cost savings.
Therefore, we expect this proposed rule to be cost neutral.
We have developed a comprehensive Preliminary Economic Analysis of
Impacts that assesses the impacts of the proposed rule. The full
preliminary analysis of economic impacts is available in the docket for
this proposed rule and at https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.
VII. Analysis of Environmental Impact
We have determined under 21 CFR 25.31(h) that this action is of a
type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
VIII. Paperwork Reduction Act of 1995
FDA tentatively concludes that this proposed rule contains no
collection of information. Therefore, clearance by the Office of
Management and Budget under the Paperwork Reduction Act of 1995 is not
required.
IX. Federalism
We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. We have determined that
this proposed rule does not contain policies that have substantial
direct effects on the States, on the relationship between the National
Government and the States, or on the distribution of power and
responsibilities among the various levels of government. Accordingly,
we conclude that the rule does not contain policies that have
federalism implications as defined in the Executive order and,
consequently, a federalism summary impact statement is not required.
X. Consultation and Coordination With Indian Tribal Governments
We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13175. We have tentatively
determined that the rule does not contain policies that would have
substantial direct effects on one or more Indian tribes, on the
relationship between the Federal Government and Indian tribes, or on
the distribution of power and responsibilities between the Federal
Government and Indian tribes. The Agency solicits comments from tribal
officials on any potential impact on Indian Tribes from this proposed
action.
XI. Reference
The following reference is on display at the Dockets Management
Staff (see ADDRESSES) and is available for viewing by interested
persons between 9 a.m. and 4 p.m. Monday through Friday; it is also
available electronically at https://www.regulations.gov. FDA has
verified the website address, as of the date this document publishes in
the Federal Register, but websites are subject to change over time.
1. FDA/Economics Staff, ``Elimination of 21 CFR 610.30 Test for
Mycoplasma, Preliminary Regulatory Impact Analysis, Preliminary
Regulatory Flexibility Analysis, Unfunded Mandates Reform Act
Analysis,'' 2018. (Available at: https://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.)
List of Subjects in 21 CFR Part 610
Biologics, Labeling, Reporting and recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act and the
Public Health Service Act, and under authority delegated to the
Commissioner of Food and Drugs, it is proposed that 21 CFR part 610 be
amended as follows:
PART 610--GENERAL BIOLOGICAL PRODUCTS STANDARDS
0
1. The authority citation for part 610 continues to read as follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360, 360c,
360d, 360h, 360i, 371, 372, 374, 381; 42 U.S.C. 216, 262, 263, 263a,
264.
Subpart D--[Removed and Reserved]
0
2. Remove and reserve subpart D, consisting of Sec. 610.30.
Dated: March 26, 2018.
Scott Gottlieb,
Commissioner of Food and Drugs.
[FR Doc. 2019-06188 Filed 4-1-19; 8:45 am]
BILLING CODE 4164-01-P